Clinical Trials List
Protocol NumberWP42004
NCT Number(ClinicalTrials.gov Identfier)NCT04580121
2020-10-01 - 2025-12-31
Phase I
Not yet recruiting1
Recruiting2
An Open-Label, Multi-Center, Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7283420 as a Single Agent in Hematologic and Molecular Relapsed/Refractory Acute Myeloid Leukemia
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Trial Applicant
-
Sponsor
Hoffmann-La Roche
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chi-Ching Chen Division of Hematology & Oncology
- Ming-Yu Lien Division of Hematology & Oncology
- Ching-Chan Lin Division of Hematology & Oncology
- Tzu-Ting Chen Division of Hematology & Oncology
- Che-Hung Lin Division of Hematology & Oncology
- Ming-Hung Tsai Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- MING YAO Division of General Internal Medicine
- - - Division of General Internal Medicine
- SHAN-CHI YU 無
- Chien-Chin Lin Division of General Internal Medicine
- Chieh-Lung Cheng Division of General Internal Medicine
- - - Division of General Internal Medicine
- Sheng-chieh Chou Division of General Internal Medicine
- Huai-Hsuan Huang Division of General Internal Medicine
- CHENG-HONG TSAI 無
- 田豐銘 Division of General Internal Medicine
- Wen-Chien Chou Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- Ya-Ping Chen Division of General Internal Medicine
- Ya-Ting Hsu Division of General Internal Medicine
- Sin-Syue Li 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Relapsed/Refractory Acute Myeloid Leukemia
Objectives
This open-label, entry-into-human (EIH) study will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of RO7283420. Escalating doses of RO7283420 will be administered to participants with Acute Myeloid Leukemia (AML) in order to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D).
The study will include AML participants with measurable disease, for whom standard-of-care (SOC) is not available. Two Groups of AML participants will be included in this study:
Group I participants will have hematologic relapse/refractory disease (participants not in CR or CRi i.e. with >=5% blast cells in the bone marrow (BM) or presence of circulating blast)
Group II participants will have molecular relapse/persistent disease (participants with a CR or CRi, and a positive MRD based on local multi-parameter flow cytometry (MFC) assessment).
The study consists of three parts:
Part A (single-participant dose escalation cohorts) - single participants from Group I will receive increment-based escalating doses until a Grade >=2 AE related to RO7283420 or a clear pharmacodynamic effect
Part B (multiple-participant dose escalation cohorts) - multiple-participant cohorts of >=3 participants will be enrolled for dose escalation for Group I and Group II independently.
Part C (dose expansion) - participants will receive the respective identified RP2D for that group.
Each participant will receive up to 6 cycles of treatment with RO7283420. At the end of Cycle 6, at the discretion of the Investigator (based on the assessment of clinical benefit), the participant could receive up to 3 additional treatment cycles.
Test Drug
RO7283420
Active Ingredient
Dasatinib
RO7283420
Tocilizumab
RO7283420
Tocilizumab
Dosage Form
injection
injection
tablet
injection
tablet
Dosage
40mg/2ml
200mg/10ml
100 mg
200mg/10ml
100 mg
Endpoints
Primary Outcome Measures :
Percentage of Participants with Adverse Events (AEs) [ Time Frame: From baseline up to 9 months ]
Percentage of Participants with Dose-Limiting Toxicities (DLTs) [ Time Frame: From baseline up to 28 days ]
Percentage of Participants with Adverse Events (AEs) [ Time Frame: From baseline up to 9 months ]
Percentage of Participants with Dose-Limiting Toxicities (DLTs) [ Time Frame: From baseline up to 28 days ]
Inclution Criteria
Inclusion Criteria:
With confirmed diagnosis of primary or secondary AML according to WHO classification 2016, with measurable disease. Eligible participants need to have received standard-of-care (SOC) and have no other SOC options available. Participants who are not willing to receive SOC will be not eligible. Two groups of participants (Group I and Group II) will be included.
Participants who have received hematopoietic stem cell transplant (HSCT) must have the HSCT performed ≥ 28 days prior to screening, having demonstrated hematological engraftment and do not have an active Graft versus Host disease
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Peripheral blast counts =< 20,000/mm3 on Cycle 1 Day 1 prior to the first dosing
Confirmed genotype of HLA-A*02
Adequate renal and liver test results
Male or female participants agree to use contraception and the abstinence requirements to prevent exposure of an embryo to the study treatment
With confirmed diagnosis of primary or secondary AML according to WHO classification 2016, with measurable disease. Eligible participants need to have received standard-of-care (SOC) and have no other SOC options available. Participants who are not willing to receive SOC will be not eligible. Two groups of participants (Group I and Group II) will be included.
Participants who have received hematopoietic stem cell transplant (HSCT) must have the HSCT performed ≥ 28 days prior to screening, having demonstrated hematological engraftment and do not have an active Graft versus Host disease
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Peripheral blast counts =< 20,000/mm3 on Cycle 1 Day 1 prior to the first dosing
Confirmed genotype of HLA-A*02
Adequate renal and liver test results
Male or female participants agree to use contraception and the abstinence requirements to prevent exposure of an embryo to the study treatment
Exclusion Criteria
Exclusion Criteria:
Acute promyelocytic leukemia (APL)
Core Binding Factor (CBF)-AML Note: participants with r/r CBF-AML after at least 2 salvage attempts can be enrolled into the study
Group II only: participants with normal karyotype and a favorable molecular profile according to ELN guideline 2017
Participants with active bacterial, fungal or viral infection considered by the Investigator to be clinically uncontrolled or of unacceptable risk upon the induction of neutropenia (i.e. participants who are or should be on antimicrobial agents for the treatment of active infection)
Glomerular proteinuria (Grade >= 2) with presence of transferrin and/or IgG in the urine
Another primary malignancy (other than AML) that requires active therapy. Adjuvant hormonal therapy is allowed
History of autoimmune disease
Clinical evidence or history of central nervous system (CNS) leukemia
Presence of isolated extramedullary disease at screening
Current or past history of CNS disease, such as stroke, CNS inflammation, epilepsy, CNS vasculitis, or neurodegenerative disease
Participants who have a history of clinically significant liver disease, including liver cirrhosis (e.g. Child-Pugh class B and C) or participants who have a history of active or chronic infectious hepatitis unless serology demonstrates clearance of infection
Participants who might refuse to receive blood products and/or have known hypersensitivity to any of the components of RO7283420
Acute promyelocytic leukemia (APL)
Core Binding Factor (CBF)-AML Note: participants with r/r CBF-AML after at least 2 salvage attempts can be enrolled into the study
Group II only: participants with normal karyotype and a favorable molecular profile according to ELN guideline 2017
Participants with active bacterial, fungal or viral infection considered by the Investigator to be clinically uncontrolled or of unacceptable risk upon the induction of neutropenia (i.e. participants who are or should be on antimicrobial agents for the treatment of active infection)
Glomerular proteinuria (Grade >= 2) with presence of transferrin and/or IgG in the urine
Another primary malignancy (other than AML) that requires active therapy. Adjuvant hormonal therapy is allowed
History of autoimmune disease
Clinical evidence or history of central nervous system (CNS) leukemia
Presence of isolated extramedullary disease at screening
Current or past history of CNS disease, such as stroke, CNS inflammation, epilepsy, CNS vasculitis, or neurodegenerative disease
Participants who have a history of clinically significant liver disease, including liver cirrhosis (e.g. Child-Pugh class B and C) or participants who have a history of active or chronic infectious hepatitis unless serology demonstrates clearance of infection
Participants who might refuse to receive blood products and/or have known hypersensitivity to any of the components of RO7283420
The Estimated Number of Participants
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Taiwan
30 participants
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Global
220 participants
